Cancer Science最新文献_第3页

Smoking-independent DNA methylation markers for lung cancer risk: External validation in a large population-based cohort study.

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-03 DOI: 10.1111/cas.16414

Zitong Zhao, Megha Bhardwaj, Ziwen Fan, Xianzhe Li, Petra Schrotz-King, Hermann Brenner

{"title":"Smoking-independent DNA methylation markers for lung cancer risk: External validation in a large population-based cohort study.","authors":"Zitong Zhao, Megha Bhardwaj, Ziwen Fan, Xianzhe Li, Petra Schrotz-King, Hermann Brenner","doi":"10.1111/cas.16414","DOIUrl":"https://doi.org/10.1111/cas.16414","url":null,"abstract":"Smoking-associated epigenetic changes have been linked to lung cancer (LC) risk; however, the role of epigenetic alterations independent of smoking is yet to be fully understood. This study aimed to validate 16 previously reported CpG sites that are independent of smoking yet associated with LC risk within a population-based prospective cohort. Using the Infinium Methylation EPIC BeadChip kit or the Infinium HumanMethylation450K BeadChip Assay, DNA methylation (DNAm) in whole blood was assessed in four subsets (n = 736, 1027, 997, and 312) of a population-based cohort from Germany. The DNAm levels of the 16 smoking-independent CpG sites were analyzed. Hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated to assess associations of DNAm at the 16 CpG sites with LC risk, adjusting for multiple covariates, including smoking habits and a smoking-associated DNAm score. Over 17 years of follow-up, a total of 199 LCs were observed. Among the 16 CpGs, cg02211449 showed a negative association with LC risk (HR [95% CI] per SD increase, = 0.70 [0.63-0.78]), while cg11385536 (1.04 [1.01-1.07]), cg09736286 (1.64 [1.10-2.44]), cg19907023 (1.64 [1.01-2.66]), and cg22032485 (1.52 [1.04-2.21]) displayed positive associations with LC risk. Five of the 16 suggested smoking-independent CpGs could be externally validated as predictors of LC risk. Further research should address their potential contribution to enhanced LC risk stratification.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatial immune heterogeneity in a mouse tumor model after immunotherapy.

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-03 DOI: 10.1111/cas.16421

Michal Smahel, Shweta Dilip Johari, Jana Smahelova, Lucie Pfeiferova, Jaroslav Nunvar

{"title":"Spatial immune heterogeneity in a mouse tumor model after immunotherapy.","authors":"Michal Smahel, Shweta Dilip Johari, Jana Smahelova, Lucie Pfeiferova, Jaroslav Nunvar","doi":"10.1111/cas.16421","DOIUrl":"https://doi.org/10.1111/cas.16421","url":null,"abstract":"Cancer immunotherapy is increasingly used in clinical practice, but its success rate is reduced by tumor escape from the immune system. This may be due to the genetic instability of tumor cells, which allows them to adapt to the immune response and leads to intratumoral immune heterogeneity. The study investigated spatial immune heterogeneity in the tumor microenvironment and its possible drivers in a mouse model of tumors induced by human papillomaviruses (HPV) following immunotherapy. Gene expression was determined by RNA sequencing and mutations by whole exome sequencing. A comparison of different tumor areas revealed heterogeneity in immune cell infiltration, gene expression, and mutation composition. While the mean numbers of mutations with every impact on gene expression or protein function were comparable in treated and control tumors, mutations with high or moderate impact were increased after immunotherapy. The genes mutated in treated tumors were significantly enriched in genes associated with ECM metabolism, degradation, and interactions, HPV infection and carcinogenesis, and immune processes such as antigen processing and presentation, Toll-like receptor signaling, and cytokine production. Gene expression analysis of DNA damage and repair factors revealed that immunotherapy upregulated Apobec1 and Apobec3 genes and downregulated genes related to homologous recombination and translesion synthesis. In conclusion, this study describes the intratumoral immune heterogeneity, that could lead to tumor immune escape, and suggests the potential mechanisms involved.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the tumor microenvironment of colorectal cancer patients post renal transplantation by single-cell analysis.

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-02 DOI: 10.1111/cas.16409

Jinghui Zhang, Yusuke Mizuuchi, Kenoki Ohuchida, Kyoko Hisano, Yuki Shimada, Naoki Katayama, Chikanori Tsutsumi, Bryan C Tan, Kinuko Nagayoshi, Koji Tamura, Takaaki Fujimoto, Naoki Ikenaga, Kohei Nakata, Yoshinao Oda, Masafumi Nakamura

{"title":"Exploring the tumor microenvironment of colorectal cancer patients post renal transplantation by single-cell analysis.","authors":"Jinghui Zhang, Yusuke Mizuuchi, Kenoki Ohuchida, Kyoko Hisano, Yuki Shimada, Naoki Katayama, Chikanori Tsutsumi, Bryan C Tan, Kinuko Nagayoshi, Koji Tamura, Takaaki Fujimoto, Naoki Ikenaga, Kohei Nakata, Yoshinao Oda, Masafumi Nakamura","doi":"10.1111/cas.16409","DOIUrl":"https://doi.org/10.1111/cas.16409","url":null,"abstract":"Patients with colorectal cancer (CRC) following renal transplantation require long-term immunosuppressants to prevent graft rejection. However, the impact of these immunosuppressants on the tumor immune microenvironment and the roles of immune cells within it remain poorly understood. We conducted comprehensive single-cell RNA sequencing on tumor and normal tissues from four CRC patients post renal transplantation and compared these with published data from 23 non-transplant CRC patients. We set four groups for detailed comparative analysis based on the renal transplantation status and tissue origin: non-renal transplantation normal (nRT_Normal), non-renal transplantation tumor (nRT_Tumor), renal transplantation normal (RT_Normal), renal transplantation tumor (RT_Tumor). Our analysis revealed significant tumor immune microenvironment landscape alterations in the transplantation group. CD8+effector T cells of RT_Tumor showed significantly diminished cytotoxicity and tumor neoantigen recognition (p < 0.0001), while CD4+FOXP3 regulatory T cells of RT_Tumor displayed a higher inhibitory score (p < 0.05), indicating preserved immunomodulatory potential compared with non-transplant CRC. Notably, significantly increased CTLA4 expression in T cells of RT_Tumor was found and testified (p < 0.05). Our findings provide novel mechanistic insights for understanding the immune landscape in renal transplant recipients with CRC and pave the way for potential immunotherapeutic strategies that may improve survival and quality of life for this patient population.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LncRNA MIR600HG inhibits laryngeal cancer development by mediating the miR-424-5p/BTG2 axis.

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-01 DOI: 10.1111/cas.16404

Xiaowen Zhu, Min Zhong, Qingdong Wang, MeiJia Zhang

{"title":"LncRNA MIR600HG inhibits laryngeal cancer development by mediating the miR-424-5p/BTG2 axis.","authors":"Xiaowen Zhu, Min Zhong, Qingdong Wang, MeiJia Zhang","doi":"10.1111/cas.16404","DOIUrl":"https://doi.org/10.1111/cas.16404","url":null,"abstract":"Laryngeal carcinoma is the predominant kind of tumor seen under the category of head and neck malignancies. LncRNA MIR600HG affects tumor morphology in numerous cancer types. However, the function of MIR600HG in laryngeal cancer remains unclear. Protein and gene expressions were analyzed by using western blot and quantitative real time polymerase chain reaction. Cells proliferation and migration were evaluated by EdU and transwell assays. Flow cytometry was performed to detect cells apoptosis. The interaction between MIR600HG or B-cell translocation gene 2 (BTG2) and miR-424-5p was analyzed by dual luciferase reporter assay and RNA immunoprecipitation. The expression of MIR600HG in laryngeal cancer tissues was lower than that in normal tissues, and low expression of MIR600HG was associated with poor prognosis in laryngeal cancer. Furthermore, overexpression of MIR600HG resulted in a reduction in cellular proliferation and the promotion of apoptosis in both HEp-2 and Tu-212. Mechanically, miR-424-5p was a direct target of MIR600HG, and overexpression of MIR600HG reduced miR-424-5p expression. Furthermore, BTG2 was a target gene of miR-424-5p and miR-424-5p upregulation suppressed the expression of BTG2. In addition, overexpression of BTG2 inhibited laryngeal cancer progression, whereas MIR600HG knockdown or miR-424-5p overexpression reversed the role of BTG2. This work suggested that MIR600HG represses laryngeal tumor development by regulating the miR-424-5p/BTG2 axis, which provides new molecules for early diagnosis of laryngeal cancer in the future.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GPNMB is a novel binding partner of FGFR1 that affects tumorigenic potential through AKT phosphorylation in TNBC.

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-28 DOI: 10.1111/cas.16419

Manar A Elhinnawi, Yukari Okita, Katsunobu Shigematsu, Mohammed Abdelaziz, Rie Shiratani, Kunio Kawanishi, Kowit Hengphasatporn, Thuy Linh Dang Cao, Yasuteru Shigeta, Mitsuyasu Kato

{"title":"GPNMB is a novel binding partner of FGFR1 that affects tumorigenic potential through AKT phosphorylation in TNBC.","authors":"Manar A Elhinnawi, Yukari Okita, Katsunobu Shigematsu, Mohammed Abdelaziz, Rie Shiratani, Kunio Kawanishi, Kowit Hengphasatporn, Thuy Linh Dang Cao, Yasuteru Shigeta, Mitsuyasu Kato","doi":"10.1111/cas.16419","DOIUrl":"https://doi.org/10.1111/cas.16419","url":null,"abstract":"Breast cancer is a heterogeneous disease and is one of the most prevalent cancers in women. Triple-negative breast cancer (TNBC) is a relatively aggressive subtype of breast cancer, which is difficult to treat. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane protein that is overexpressed in various types of cancers, including breast cancer, especially TNBC. In this study, bioinformatic analyses revealed enhanced fibroblast growth factor receptor 1 (FGFR1) signaling in patients with invasive breast cancer, and the GPNMBhigh/FGFR1high group exhibited a lower probability of relapse-free survival (RFS) than the GPNMBlow/FGFR1low group. Additionally, we observed that GPNMB and FGFR1 were essential for sphere formation, cellular migration, and epithelial-mesenchymal transition (EMT)-like changes in TNBC cells. To explore the mutual interaction between these two molecules, we conducted in silico protein-protein docking studies and molecular dynamics simulations. The results revealed that GPNMB isoform b exhibits high binding affinity for FGFR1 isoform c (FGFR1c), which correlates with cancer aggressiveness. We also confirmed the interaction between GPNMB and FGFR1 in TNBC cells. Furthermore, our study demonstrated that GPNMB is essential for AKT phosphorylation at T308 following FGF2 stimulation, resulting in high affinity for FGFR1c. Inhibition of AKT phosphorylation substantially reduces the tumorigenic potential of TNBC cells.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Projection of future gastric cancer incidence and health-care service demand by geographic area in Kanagawa, Japan.

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-28 DOI: 10.1111/cas.16415

Choy-Lye Chei, Sho Nakamura, Kaname Watanabe, Ryo Watanabe, Akio Kurokawa, Taizo Iwane, Sayaka Itoh, Hiroto Narimatsu

{"title":"Projection of future gastric cancer incidence and health-care service demand by geographic area in Kanagawa, Japan.","authors":"Choy-Lye Chei, Sho Nakamura, Kaname Watanabe, Ryo Watanabe, Akio Kurokawa, Taizo Iwane, Sayaka Itoh, Hiroto Narimatsu","doi":"10.1111/cas.16415","DOIUrl":"https://doi.org/10.1111/cas.16415","url":null,"abstract":"Projections of future gastric cancer incidence and the demand for health-care services for gastric cancer patients by geographic area will assist local authorities in determining health-care needs, allocating medical resources, and planning services. This study aims to project the future incidence of gastric cancer, estimate the number of patients per medical institution, and decompose the net changes in cases to assess the impact of population aging by geographic area. Our projections are based on population-based cancer registry data, census data from 2000 to 2020, and the projected population for 2025-2045 in Kanagawa, Japan. We classified Kanagawa into urban, town, outer city, and rural areas based on geographic and population features. The number of medical institutions providing gastric cancer treatment was used to estimate the number of patients per medical institution. We projected a decrease of 25%, 52%, and 5% in gastric cancer cases in towns, outer cities, and rural areas from 2020 to 2045, respectively. However, cases are expected to increase by 9% in urban areas, primarily due to population aging. The annual number of gastric cancer patients per medical institution in urban areas is expected to increase from 54 to 59, while numbers in other areas are predicted to decline from 2020 to 2045. Our long-term projections indicate that the number of older gastric cancer patients will continue to increase in urban areas. While current measures effectively reduce gastric cancer risk, they need to be revised to address the impact of population aging.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PD-1 blockade treatment in melanoma: Mechanism of response and tumor-intrinsic resistance. 黑色素瘤的 PD-1 阻断治疗：反应机制和肿瘤内在抗药性。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-27 DOI: 10.1111/cas.16398

Tong Wang, Wenjie Ma, Zijian Zou, Jingqin Zhong, Xinyi Lin, Wanlin Liu, Wei Sun, Tu Hu, Yu Xu, Yong Chen

引用次数: 0

Fibrous corona is reduced in cancer cell lines that attenuate microtubule nucleation from kinetochores. 癌症细胞系中的纤维电晕会减少，因为它们会减弱来自动点的微管成核。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-27 DOI: 10.1111/cas.16406

Yudai Ishikawa, Hirotaka Fukue, Runa Iwakami, Masanori Ikeda, Kenji Iemura, Kozo Tanaka

{"title":"Fibrous corona is reduced in cancer cell lines that attenuate microtubule nucleation from kinetochores.","authors":"Yudai Ishikawa, Hirotaka Fukue, Runa Iwakami, Masanori Ikeda, Kenji Iemura, Kozo Tanaka","doi":"10.1111/cas.16406","DOIUrl":"https://doi.org/10.1111/cas.16406","url":null,"abstract":"Most cancer cells show increased chromosome missegregation, known as chromosomal instability (CIN), which promotes cancer progression and drug resistance. The underlying causes of CIN in cancer cells are not fully understood. Here we found that breast cancer cell lines show a reduced kinetochore localization of ROD, ZW10, and Zwilch, components of the fibrous corona, compared with non-transformed breast epithelial cell lines. The fibrous corona is a structure formed on kinetochores before their end-on attachment to microtubules and plays a role in efficient kinetochore capture and the spindle assembly checkpoint. The reduction in the fibrous corona was not due to reduced expression levels of the fibrous corona components or to a reduction in outer kinetochore components. Kinetochore localization of Bub1 and CENP-E, which play a role in the recruitment of the fibrous corona to kinetochores, was reduced in cancer cell lines, presumably due to reduced activity of Mps1, which is required for their recruitment to kinetochores through phosphorylating KNL1. Increasing kinetochore localization of Bub1 and CENP-E in cancer cells restored the level of the fibrous corona. Cancer cell lines showed a reduced capacity to nucleate microtubules from kinetochores, which was recently shown to be dependent on the fibrous corona, and increasing kinetochore localization of Bub1 and CENP-E restored the microtubule nucleation capacity on kinetochores. Our study revealed a distinct feature of cancer cell lines that may be related to CIN.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pan-immune-inflammation value predicts immunotherapy response and reflects local antitumor immune response in rectal cancer. 泛免疫炎症值可预测免疫疗法反应并反映直肠癌的局部抗肿瘤免疫反应。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-27 DOI: 10.1111/cas.16400

Qianyu Wang, Wentao Zhong, Yi Xiao, Guole Lin, Junyang Lu, Lai Xu, Guannan Zhang, Aijun Liu, Junfeng Du, Bin Wu

{"title":"Pan-immune-inflammation value predicts immunotherapy response and reflects local antitumor immune response in rectal cancer.","authors":"Qianyu Wang, Wentao Zhong, Yi Xiao, Guole Lin, Junyang Lu, Lai Xu, Guannan Zhang, Aijun Liu, Junfeng Du, Bin Wu","doi":"10.1111/cas.16400","DOIUrl":"https://doi.org/10.1111/cas.16400","url":null,"abstract":"The pan-immune-inflammation value reflects the systemic inflammatory response, and tumor-infiltrating lymphocytes indicate a local immune response in rectal cancer. However, the association between systemic inflammatory response, as indicated by the pan-immune-inflammation value, and local immune responses in rectal cancer remains unclear. This study analyzed 915 treatment-naïve rectal cancer patients from the Peking Union Medical College Hospital and PLA General Hospital (PLAGH) cohorts who underwent radical surgery to investigate the relationship between the pan-immune-inflammation value and immune responses. Lower pan-immune-inflammation value was significantly associated with improved disease-free survival and cancer-specific survival. Multivariate Cox regression models identified the pan-immune-inflammation value as an independent prognostic factor. In the PLAGH cohort, patients with low pan-immune-inflammation values had higher immune cell levels, activated immune pathways, and increased expression of immune checkpoint genes according to RNA sequencing. Hematoxylin and eosin staining and immunohistochemical analysis revealed that lower pan-immune-inflammation value was associated with higher tumor-infiltrating lymphocyte density, more mature tertiary lymphoid structures, increased CD8+ T cells, and elevated human lymphocyte antigen class I expression. Conversely, patients with high pan-immune-inflammation values exhibited pathways linked to tumor progression, such as angiogenesis, epithelial-mesenchymal transition, hypoxia, KRAS signaling, and TGF-ß signaling. Among patients receiving anti-PD-1 therapy, responders had low pre- and post-treatment pan-immune-inflammation values. The pan-immune-inflammation value is a reliable marker associated with distinct immune microenvironment characteristics and can effectively predict disease-free survival, cancer-specific survival, and response to immunotherapy.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TRIM47 promotes hypopharyngeal and laryngeal cancers progression through promoting K63-linked ubiquitination of vimentin. TRIM47 通过促进与 K63 链接的波形蛋白泛素化来促进下咽癌和喉癌的进展。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-11-25 DOI: 10.1111/cas.16397

Shichao Qin, Fen Chang, Xiangkai Sun, Zinan Li, Yin Wang, Dapeng Lei

{"title":"TRIM47 promotes hypopharyngeal and laryngeal cancers progression through promoting K63-linked ubiquitination of vimentin.","authors":"Shichao Qin, Fen Chang, Xiangkai Sun, Zinan Li, Yin Wang, Dapeng Lei","doi":"10.1111/cas.16397","DOIUrl":"https://doi.org/10.1111/cas.16397","url":null,"abstract":"Hypopharyngeal and laryngeal cancers which belong to head and neck squamous cell carcinoma (HNSCC) are the two most malignant types of head and neck cancer, characterized by a low 5-year survival rate, high recurrence and metastasis rate. It is vital to explore strategies to suppress metastasis and improve prognosis for patients with these cancers. In this research, we analyzed the clinical data and found that E3 ubiquitin ligase TRIM47 was upregulated in cancer tissues of hypopharyngeal cancer and was closely associated with poor survival outcomes. In terms of mechanism, we performed tandem affinity chromatography and denatured Ni-NTA Agarose pulldown. As a result, TRIM47 was found to interact with vimentin and control vimentin stabilization through ubiquitination, specifically in the form of K63 chains. Importantly, through experiments of cancer cell viability and migration, we found that TRIM47 could enhance the proliferation and metastasis abilities of cancer cells in a vimentin-dependent manner, thus promoting the advancement of hypopharyngeal and laryngeal cancers. TRIM47 was verified to regulate cancer cells metastasis in vivo using metastasis models. All these results imply that TRIM47 emerges as a potential biomarker for early diagnosis and metastasis prediction of hypopharyngeal and laryngeal cancers and represents a promising therapeutic target.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0